The objective of our work is to understand the influences affecting the metabolic capacity of skeletal muscle. While it is clear that innervation is a critical element in normal development and maintenance of muscle, the extent to which innervation can dominate over factors intrinsic to muscle and its environment, and indeed, the nature of the neural control remains unclear. Fundamental aspects of the neural influences on muscle will be addressed under four major topics: 1) Biochemical differentiation during development; 2) Biochemical transformations in mature muscle, particularly with artificial stimulation and exercise; 3) The correlation of muscle biochemistry and the physiological properties of the parent nerve; 4) The biochemical nature of muscle diseases including those with alterations of the nervous system. In this research we propose to circumvent an inherent complication in the study of nerve-muscle interactions. Skeletal muscle is an intimate mixture of highly specialized fibers which differ greatly in biochemical properties. Fibers lying next to each other may vary as much as 50-fold in some enzyme concentrations, thereby limiting the usefulness of whole muscle studies. The analytical methods employed here provide the capability to analyze individual fibers and, thus, eliminate the problems of interpretation of whole muscle data. A new technique has been developed to measure enzymes in single fibers identified morphologically and histochemically in cross-sections. This in situ identification provides a means to select for study fibers of a given type or to select affected fibers in diseased muscle in which most of the fibers may be unaffected. In addition, it allows the direct comparison of other characteristics of muscle that can be measured in cross-section, particularly those identifiable with specific antibody staining techniques.